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How are gastrointestinal carcinoid tumors diagnosed?

If you have symptoms that might be from a gastrointestinal (GI) carcinoid tumor, you should see a doctor. He or she will take your medical history and examine you. If the doctor suspects some type of tumor or cancer, some tests will be ordered.

Medical history and physical exam

In taking your medical history, the doctor asks you questions about your general health, lifestyle habits, symptoms, and risk factors. The doctor also will probably ask about symptoms of the carcinoid syndrome, as well as symptoms that might be caused by a mass (tumor) in the stomach, intestines, or rectum.

Some patients with neuroendocrine tumors also have cancers or benign tumors of other organs, so doctors may ask about symptoms that might suggest other tumors are present. A thorough physical exam will provide information about signs of neuroendocrine tumors and other health problems. The doctor may pay special attention to the abdomen, looking for a tumor mass or enlarged liver.

If your medical history and physical exam give the doctor reason to suspect you might have a GI carcinoid, some tests will be ordered to find out if the disease is present.

Imaging tests

Your doctor may order one or more types of imaging tests to help determine the cause of your symptoms.

Barium x-ray

These tests use a barium-containing solution that coats the lining of the esophagus, stomach, and intestines. The coating of barium helps show abnormalities of the lining of these organs. This type of study is often useful in diagnosing some GI carcinoid tumors. It is least effective in finding small intestine carcinoids.

Barium studies can be used to examine the upper or lower parts of the digestive system. You will probably not be able to eat or drink anything (other than water) the night before the test. If the colon is being examined, you may need to take laxatives and/or enemas to cleanse the bowel the night before or the morning of these exams.

Barium swallow: This test is used to examine the lining of the esophagus. The patient drinks a barium solution that coats the lining of the esophagus. Then x-ray pictures are taken.

Upper GI series: This test is used to examine the lining of the stomach and the first part of the small intestine. The patient swallows the barium solution, and then may be moved around a bit so that it coats the inside of the stomach. Over time, it will leave the stomach and coat the first part of the small intestine. More x-rays can be taken over the next few hours as the barium travels through the rest of the small intestine. This is called a small bowel follow-through.

Enteroclysis: This is another way to look at the small intestine. In this test, a thin tube is passed from the mouth or nose down through the stomach to the start of the small intestine. Barium contrast is sent through the tube, along with a substance that creates more air in the intestines, causing them to expand. X-rays of the intestines are then taken. This test may be quicker and give clearer images of the small intestine than a small bowel follow-through, but the use of a tube to give the barium makes it more uncomfortable.

Barium enema: This test (also known as a lower GI series) is used to look at the inner surface of the colon and rectum. The barium solution is given as an enema (through the anus) while the patient is lying on the x-ray table. When the colon is about half full of barium, the patient rolls over so the barium spreads throughout the colon. Then x-rays are taken. After the barium is put in, air may be blown in to help spread the barium toward the bowel wall and better coat the inner surface. This is called an air contrast (or double contrast) barium enema. X-rays are then taken.

Barium x-rays are used less these days than in the past. In many cases they are being replaced by endoscopy, where the doctor actually looks into the esophagus, stomach, or colon with a narrow fiber optic scope.

Computed tomography (CT) scan

A CT scan can help tell if the cancer has spread into your lymph nodes or other organs such as your liver.

The CT scan uses x-rays to make detailed cross-sectional images of your body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these into images that look like slices of the part of your body that is being studied.

Before any pictures are taken, you might be asked to drink 1 to 2 pints of a liquid called oral contrast. This helps outline the intestine so that certain areas are not mistaken for tumors. You might also receive an IV (intravenous) line through which a different kind of contrast dye (IV contrast) is injected. This helps better outline structures in your body. The injection can cause some flushing (redness and warm feeling that may last hours to days). A few people are allergic to the dye and get hives. Rarely, more serious reactions like trouble breathing and low blood pressure can occur. Medicine can be given to prevent and treat allergic reactions. Be sure to tell the doctor if you have any allergies (especially to iodine or shellfish) or if you have ever had a reaction to any contrast material used for x-rays.

A CT scanner has been described as a large donut, with a narrow table that slides in and out of the middle opening. You will need to lie still on the table while the scan is being done. CT scans take longer than regular x-rays, and you might feel a bit confined by the ring while the pictures are being taken.

When GI carcinoid tumors spread, it is often to the liver. To see if there are areas of cancer spread in the liver, a special type of CT known as a 3D-, 4D-, or multiphase CT scan is done. This means having one set of CT images taken before IV contrast is given. Then more sets of scans are taken as the contrast passes through the liver.

CT scans can also be used to guide a biopsy needle precisely into a suspected area of cancer spread. For a CT-guided needle biopsy, you remain on the CT scanning table, while a doctor moves a biopsy needle through the skin and toward the mass. CT scans are repeated until the doctor is sure that the needle is in the mass. A fine-needle biopsy sample (tiny fragment of tissue) or a core-needle biopsysample (a larger cylinder of tissue) is removed and looked at under a microscope.

Magnetic resonance imaging (MRI) scan

MRI scans use radio waves and strong magnets instead of x-rays to create detailed images of parts of the body. Like a CT scan, an MRI produces cross-sectional slices of the body. As with a CT scan, a contrast material might be injected into a vein, but it is not needed as often.

MRI scans take longer than CT scans, often up to an hour. You may have to lie inside a narrow tube which can feel confining and can upset people with a fear of enclosed spaces. Special, open MRI machine can help with this if needed, although the images might not be as sharp in some cases. The MRI machine makes loud buzzing noises, but some places provide headphones to help block the sound.

Sometimes MRI is used to look at blood vessels in the liver. This requires IV contrast and is known as MR angiography (MRA).

Radionuclide scans

Scans using small amounts of radioactivity and special cameras can be helpful in looking for carcinoid tumors. They can help determine the extent of the tumor, as well as help locate it if doctors aren’t sure where it is in the body.

Somatostatin receptor scintigraphy (OctreoScan®): This is the scan most often used to look for carcinoid tumors. For this scan, a radioactive substance called indium-111 is bound to a hormone-like substance called octreotide. When a small amount of this combined substance is injected into the blood, the octreotide causes it to attach to proteins on carcinoid cells. About 4 hours after the injection, a special camera can be used to show where the radioactivity has collected in the body. More scans may be done over the next few days as well.

I-131 MIBG scan: This is another test that can be used to find carcinoid tumors, but it is used less often than the OctreoScan. This test uses a chemical called MIBG that has radioactive iodine (I-131) attached. This substance is injected into a vein, and the body is scanned several hours or days later with a special camera to look for areas that picked up the radioactivity. These would most likely be carcinoid tumors, although other kinds of neuroendocrine tumors will also pick up this chemical.

Positron emission tomography (PET) scan

A PET scan is another imaging test that uses low levels of radioactivity to look for tumors. PET scans usually use a form of radiolabeled glucose (sugar) to find tumors. But to look for neuroendocrine tumors/cancers, a special type of PET scan is done, using a radioactive form of 5-hydroxytryptophan (5-HTP). This chemical is injected into the bloodstream and is taken up and used by carcinoid cells. After about an hour, a special camera is used to find the areas of radioactivity. Some doctors have found this type of PET scan to be more accurate than CT scans for detecting spread of disease. However, this type of PET scan is not available in every hospital (even some hospitals that have a PET scanner).

Endoscopy

Endoscopy tests use a flexible lighted tube (endoscope) with a video camera on the end. The camera is connected to a monitor, which lets the doctor see any abnormal areas in the lining of the digestive organs clearly. If needed, small pieces of the abnormal areas can be removed (biopsied) through the endoscope. The biopsy samples can be looked at under the microscope to find out if cancer is present and what kind of cancer it is.

Upper endoscopy

This test is also known as esophogogastroduodenoscopy or EGD. An endoscope is passed down through the mouth to look at the esophagus, stomach, and first part of the small bowel.

An upper endoscopy may be done in a hospital outpatient department, clinic, or doctor’s office. It usually takes 15 to 30 minutes, and most patients are given intravenous medicine to make them feel relaxed and sleepy. If you are sedated for the procedure, you will need someone to take you home (not just a cab).

Colonoscopy

This test is also called lower endoscopy. A special endoscope known as a colonoscope is inserted through the anus up into the colon. The doctor will be able to see the lining of the entire rectum and colon. For a clear view though, the colon must be completely cleaned out before the test. There are different ways to do this, but the most common is drinking a large amount of a laxative solution the night and the morning of the exam.

You will be given intravenous medicine to make you feel relaxed and sleepy during the procedure. A colonoscopy can be done in a hospital outpatient department, clinic, or doctor's office. It usually takes 15 to 30 minutes, although it may take longer if a tumor is seen and/or a biopsy is taken. Because you will be sedated for the procedure, you will need someone you know to take you home afterward.

Proctoscopy

Proctoscopy can be used to look for a rectal tumor. This test uses a shorter, rigid, hollow tube (a proctoscope), which is about 10 inches long and about 1 inch across and may have a light on the end of it. The doctor coats the proctoscope with a lubricant and then gently pushes it into the anus and rectum. By shining a light into this tube, the doctor has a clear view of the lining of the rectum and anus. This test usually requires that you take laxatives or have an enema beforehand to make sure the bowels are empty.

Capsule endoscopy

Unfortunately, neither upper nor lower endoscopy can reach all areas of the small intestine, where many carcinoid tumors begin. A technique known as capsule endoscopy may help in some cases.

This test doesn’t really use an endoscope. Instead, the patient swallows a capsule (about the size of a large vitamin pill) that contains a light source and a tiny camera. Like any other pill, the capsule goes through the stomach and into the small intestine. As it travels (usually over about 8 hours), it takes thousands of pictures. These images are transmitted electronically to a device worn around the person’s waist, while he or she goes on with normal daily activities. The pictures can then be downloaded onto a computer, where the doctor can watch them as a video. The capsule passes out of the body during a normal bowel movement and is discarded.

Double balloon enteroscopy

This is another way to look at the small intestine. The small intestine is too long (20 feet) and has too many curves to be examined well with regular endoscopy. This method gets around these problems by using a special endoscope that is made up of 2 tubes, one inside the other. First the inner tube, which is an endoscope, goes forward about a foot, and then a balloon at its end is inflated to anchor it. Then the outer tube goes forward to near the end of the inner tube and it is then anchored in place with a balloon. This process is repeated over and over, letting the doctor see the intestine a foot at a time.

This procedure is done after the patient is given drugs to make him or her sleepy and may be even done under general anesthesia (where the patient is asleep). The main advantage of this test over capsule endoscopy is that the doctor can take a biopsy if something abnormal is seen. As with other tests that are done under sedation, you will need someone to take you home after this procedure (not just a cab).

Endoscopic ultrasound (EUS)

This test uses an endoscope with a small ultrasound probe on the end. This probe releases sound waves and then uses the echoes that bounce back to create images of the digestive tract wall (or nearby lymph nodes). Putting the ultrasound probe on the end of an endoscope lets it get very close to a tumor. Because the probe is close to the area being looked at, it can make very detailed pictures.

EUS can be used to see how deeply a tumor has grown into the wall of the esophagus, stomach, intestine, or rectum. It can also help see if certain lymph nodes are enlarged and help a doctor guide a needle into lymph node, tumor, or other suspicious area to do a biopsy. You will be sedated for this test, so you will need someone to take you home (not just a cab).

Biopsy

Even if an imaging test finds a mass, it can’t tell if the mass is a carcinoid tumor, some other type of tumor, or an area of infection. The only way to know for sure is to remove cells from the abnormal area and look at them under a microscope. This procedure is called a biopsy.

There are several ways to take a sample from a GI tumor. One way is through the endoscope. When a tumor is found, the doctor can use biopsy forceps (pincers or tongs) through the tube to take a small sample of it. Another way to sample a tumor is with a CT-guided needle biopsy, as described in the section on CT scans.

Bleeding after a biopsy of a GI carcinoid is a rare but potentially serious problem. If serious bleeding occurs, doctors can sometimes inject drugs into the tumor to constrict blood vessels and slow or stop bleeding.

In rare cases, neither endoscopic biopsy nor a CT-guided needle biopsy will be able to get enough tissue to identify the type of tumor. This is sometimes the case with tumors in the small intestine. In such cases, surgery may be needed to remove a tissue sample.

Blood and urine tests

Blood and urine tests can be very helpful in diagnosing carcinoid syndrome in patients who have symptoms that might be caused by it.

Many carcinoid tumors, especially those in the small intestine, make serotonin (also called 5-HT). It is probably the cause of at least some of the symptoms of carcinoid syndrome. The body breaks it down into 5-hydroxyindoleactic acid (5-HIAA), which is released into the urine. A common test to look for carcinoid syndrome measures the levels of 5-HIAA in a urine sample collected over 24 hours. Measuring the serotonin levels in the blood may also give useful information. These tests can help diagnose many (but not all) carcinoid tumors. Sometimes, the tumors are small and don’t release enough serotonin for a positive test result.

In other cases, the tumors do not make much serotonin, but they do make its precursor, 5-HTP, which can be converted to serotonin in the urine. In patients with these tumors, the blood serotonin level may be normal, but the urine levels of serotonin and 5-HTP are high.

Some foods, including bananas, plantains, kiwi fruit, certain nuts, avocado, tomatoes, and eggplant, contain a lot of serotonin and can raise 5-HIAA levels in the urine. Medicines, including cough syrup and acetaminophen (Tylenol), can also affect the results. Ask your doctor what you should avoid before having urine or blood tests for carcinoids.

Other common tests to look for carcinoids include blood tests for chromogranin A (CgA), neuron-specific enolase (NSE), substance P, and gastrin. Medicines that lower stomach acid called proton-pump inhibitors (such as omeprazole/Prilosec®, lansoprazole/Prevacid®, esomeprazole/Nexium®, and many others) can make CgA and gastrin levels high even when carcinoid tumors aren’t present. If you take any of these medicines, talk to your doctor about what you need to avoid before having these blood tests. Depending on the tumor’s location and your symptoms, your doctor might do other blood tests as well.

Some of these tests can also be used to show how well treatment is working, since the levels of these substances tend to go down as tumors shrink.